Structural highlights
Function
[A1Z0P7_HHV1] Envelope glycoprotein that forms spikes at the surface of virion envelope. Essential for the initial attachment to heparan sulfate moities of the host cell surface proteoglycans. Involved in fusion of viral and cellular membranes leading to virus entry into the host cell. Following initial binding to its host receptors, membrane fusion is mediated by the fusion machinery composed at least of gB and the heterodimer gH/gL. May be involved in the fusion between the virion envelope and the outer nuclear membrane during virion egress.[HAMAP-Rule:MF_04032]
Publication Abstract from PubMed
Cell entry of enveloped viruses requires specialized viral proteins that mediate fusion with the host membrane by substantial structural rearrangements from a metastable pre- to a stable postfusion conformation. This metastability renders the herpes simplex virus 1 (HSV-1) fusion glycoprotein B (gB) highly unstable such that it readily converts into the postfusion form, thereby precluding structural elucidation of the pharmacologically relevant prefusion conformation. By identification of conserved sequence signatures and molecular dynamics simulations, we devised a mutation that stabilized this form. Functionally locking gB allowed the structural determination of its membrane-embedded prefusion conformation at sub-nanometer resolution and enabled the unambiguous fit of all ectodomains. The resulting pseudo-atomic model reveals a notable conservation of conformational domain rearrangements during fusion between HSV-1 gB and the vesicular stomatitis virus glycoprotein G, despite their very distant phylogeny. In combination with our comparative sequence-structure analysis, these findings suggest common fusogenic domain rearrangements in all class III viral fusion proteins.
The prefusion structure of herpes simplex virus glycoprotein B.,Vollmer B, Prazak V, Vasishtan D, Jefferys EE, Hernandez-Duran A, Vallbracht M, Klupp BG, Mettenleiter TC, Backovic M, Rey FA, Topf M, Grunewald K Sci Adv. 2020 Sep 25;6(39). pii: 6/39/eabc1726. doi: 10.1126/sciadv.abc1726., Print 2020 Sep. PMID:32978151[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Vollmer B, Prazak V, Vasishtan D, Jefferys EE, Hernandez-Duran A, Vallbracht M, Klupp BG, Mettenleiter TC, Backovic M, Rey FA, Topf M, Grunewald K. The prefusion structure of herpes simplex virus glycoprotein B. Sci Adv. 2020 Sep 25;6(39). pii: 6/39/eabc1726. doi: 10.1126/sciadv.abc1726., Print 2020 Sep. PMID:32978151 doi:https://dx.doi.org/10.1126/sciadv.abc1726
